BACKGROUND This study aimed to explore the features of cognitive impairment in patients with neurosyphilis at the early stage of mild cognitive impairment (MCI). MATERIAL AND METHODS A total of 18 patients with asymptomatic neurosyphilis (ANS), 19 patients with neurosyphilis at the MCI stage (neurosyphilis-MCI), and 15 patients with neurosyphilis at the dementia stage (neurosyphilis-dementia) were enrolled. Cognitive function was evaluated using comprehensive rating scales. Tests of syphilis in blood and cerebrospinal fluid (CSF) were conducted, and white blood cell (WBC) counts and protein levels in CSF were measured. RESULTS Overall cognitive function and individual cognitive domains, including memory, language, visuospatial skill, and attention/executive function, were all significantly impaired in the neurosyphilis-MCI group compared with the ANS group, and were further impaired in the neurosyphilis-dementia group. Although there was no difference in serum rapid plasma regain (RPR) titer among the 3 groups, the number of patients with serum RPR titer ≥1: 32 in the neurosyphilis-MCI group was much higher than that in the ANS group. CSF RPR positive rate in the neurosyphilis-MCI group was significantly higher than that in the ANS group. The WBC count, protein level, and the rate of elevated protein level or increased WBC count in CSF did not differ among the 3 groups. CONCLUSIONS The feature of cognitive impairment of neurosyphilis-MCI patients displayed multiple-domain amnestic MCI. Perhaps there were extensive brain areas involved at the early stage, and a continuous neuroinflammatory process was through the different stages of neurosyphilis. Early diagnosis and treatment are very important for preventing the progression of general paresis of the insane.